Epidemiologic evidence has been accumulating that smoking is causally related to cancers of the larynx, oral cavity, and esophagus in both men and women. The mortality ratios for these cancers are similar for smokers of cigarettes, pipes, or cigars. A strong dose-response relationship exists. Compared with those who continue smoking, the risk of cancer decreases for those who quit smoking. Alcohol consumption is also an important risk factor for oral, pharyngeal, laryngeal, and esophageal cancer. The combination of smoking and alcohol acts synergistically to increase risk of these cancers. The purpose of this study is to re-examine these relationships using recent large national data sets and examine the possible physiologic mechanisms through which smoking acts on oral tissue (for example, there is some evidence that neutrophil disfunction is related to smoking).